TABLE 1.
Compounds divided into two classes based on the aromatic linker
| Class and compounda | Aromatic linker | EC50b (μM) after treatment for: |
EC5048/EC5096 ratio | Stage of actionc | |
|---|---|---|---|---|---|
| 48 h | 96 h | ||||
| Class 1 | |||||
| 28 | Pyrimidine | 0.168 (0.011) | 0.038 (0.012) | 4.4 | Late schizont |
| 31 | Pyrimidine | 1.663 (0.650) | 0.238 (0.047) | 7.0 | Late schizont |
| 35 | Pyrimidine | >1,000 | 0.809 (0.451) | >1,000 | Late schizont |
| 36 (Cpd A) | Pyrimidine | >1,000 | 0.023 (0.007) | >1,000 | Late schizont |
| 38 | Pyrimidine | >1,000 | 0.050 (0.018) | >1,000 | Late schizont |
| 39 (Cpd B) | Pyrimidine | >1,000 | 0.020 (0.008) | >1,000 | Late schizont |
| 41 (Cpd C) | Pyrimidine | >1,000 | 0.037 (0.005) | >1,000 | Late schizont |
| Class 2 | |||||
| 7 (Cpd D) | Pyridine | 0.355 (0.083) | 0.311 (0.103) | 1.1 | Trophozoite |
| 20 (Cpd E) | Fluoropyridine | 0.298 (0.066) | 0.142 (0.024) | 2.1 | Trophozoite |
| 22 | Pyridine | 0.546 (0.080) | 0.300 (0.141) | 1.8 | Trophozoite |
a
Class 1, pyrimidine linker; class 2, nonpyrimidine linker. Cpd, compound
b
EC50s of compounds were determined using a SYBR green I assay following treatment of parasite cultures with serial dilutions of the compounds for 48 h or 96 h. Data presented show the mean EC50 values from three independent experiments, with the standard deviations shown in parentheses.
c
The stage of action was determined by microscopic examination of Giemsa-stained parasite smears after treatment of ring stage parasites with 10 times the 96-h EC50 of compound for 48 h.